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Case Western Center for Global Health and Diseases' growth adds jobs in Cleveland, as researchers work to eradicate illnesses worldwide

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Case Western Reserve's Center for Global Health and Diseases is part of the school's School of Medicine, and is home to nine full-time faculty members, who this year brought in $10 million in research funding for their work in diseases that affect the developing world.
(Plain Dealer file)

CLEVELAND, Ohio -- The researchers at Case Western Reserve University’s Center for Global Health and Diseases work on a lot of illnesses that most of us barely ever think about. And if we’re honest, diseases we don’t care much about either. Diseases that make us uncomfortable, such as HIV and AIDS, and squeamish, such as infections with parasitic snails and worms.

When they’re not in Cleveland, they work in parts of the world that are remote, poor, and often road-less. They see people suffering and dying from treatable and preventable illnesses. Their goal, quite simply, is “to make life better in developing countries.”

Now, the center's director may have fulfilled a goal that began in 1983, to find an effective, simple way to eliminate a widespread, mosquito-borne illness.

That would only bolster the researchers' reputation -- internationally and here at home, where the Center has become an economic driver for the university and the city. Since the center’s opening in 2002, researchers have nearly doubled their annual grant funding from $5.6 million to $10 million this year, three new full-time faculty members have joined the original staff of six, and the center filled five new administrative positions.

The Center, which is currently involved in 32 ongoing projects overseas, has secured more than $80 million in funding, mostly from the National Institutes of Health (NIH) and The Bill and Melinda Gates Foundation, since its creation.

“The [grants] support from about 50 to 80 percent of a faculty member’s salary,” said Dr. James Kazura, director of the center. The grants also fund between 25 and 30 technicians, he said.

Grant funding also supplies resources to train graduate students from Case and foreign students from countries where the Center has ties (such as Papua New Guinea, Kenya and Brazil), who come to Case to receive Master’s degrees.

“This is an economic engine for Case and for Cleveland,” said Kazura. “It’s a revenue generator and it develops intellectual capital here.”

Kazura’s work – a decades-long search for a way to eliminate a debilitating mosquito-borne illness that affects more than 100 million people -- has been one of the main drivers of the center’s growth, accounting for 15 to 20 percent of research grants. Their research, published several times in the New England Journal of Medicine and the Lancet, has received international attention for its value in advancing the public health goal of eradication of the disease, called lymphatic filariasis.

His most recent study was published online Aug. 22 in the New England Journal of Medicine.

The study details the center’s success in cutting down transmission of the disease, an infection caused by a mosquito-borne parasite that leads to fever, malnutrition and a grotesque swelling of the limbs and genitals. It is commonly known by the name “elephantiasis” for this reason.

Dr. James KazuraCase Western Reserve University

Kazura and his team began their work battling lymphatic filariasis in Papua New Guinea in 1983. Papua New Guinea, an island nation of about 7 million people north of Australia, has one of the highest rates of lymphatic filariasis infection in the world. More than 120 million worldwide suffer from the disease, according to the World Health Organization (WHO), primarily in poor tropical and sub-tropical regions.

“When we started in Papua New Guinea, it was thought that filariasis was untreatable,” Kazura said. “There were no drugs that we knew were safe, and nothing that would cure infection,” and efforts to control the mosquito population in areas of poor drainage and open sewers had been an utter failure.

People were bitten by an average of 40,000 to 50,000 mosquitoes a year in the villages Kazura worked in.

Lymphatic filariasis is a disease of the lymph system caused by infestation of the lymphatic vessels by tiny threadlike worms (filiariae). It is rarely life-threatening, but is chronic, and causes significant pain, disability and social stigma. Infection usually occurs in childhood, but symptoms often don’t appear for years. Mosquitoes that bite an infected person then pick up the parasitic worms and pass them on to other people.

Kazura said that data from China, released when that country eased some of its restrictions on sharing scientific research, offered the first hope for potentially treating the disease, in the form of an annual treatment with one anti-parasitic drug.

In 1993, Kazura and his team began a five-year study of a highly-infected population of 2,500 villagers to see if using two anti-parasitic drugs, ivermectin (which may sound familiar to dog owners as a heartworm treatment) and diethylcarbamazine, once a year for four years, would work to eliminate the disease.

They published their results, which were even better than they had hoped for, in the New England Journal of Medicine in 2002. The proportion of people testing positive for the infection decreased by 86 to 98 percent, the rate of mosquito transmission decreased substantially, and new infections in children were almost completely prevented during the five-year study period.

“The notion was that [drug treatment] would lower the number of these worms in the blood so that even though the mosquitoes that were transmitting it continued to bite, there were too few of the parasites so new infections could be stopped or slowed down,” Kazura said.

In short, the drug treatment worked. And at about a penny a dose, it was cheap.

Still, Kazura said it soon became clear that mass drug treatment alone would not be enough. In 2007, he and his team got another NIH research grant and returned to Papua New Guinea to figure out just how long they would need to administer the drugs, and to what percentage of the population, to halt transmission completely.

“This is a big issue in infectious disease, because nobody’s going to support this indefinitely,” he said. “We showed that five years of 80 percent coverage wasn’t enough. It’s like getting a vaccine every year — you need 80 to 90 percent coverage. That’s not going to work in Papua New Guinea, and it’s not going to work in Cleveland Heights either, because people are just not going to participate in it. And there will be donor fatigue.”

Fortunately, their research took a serendipitous turn. A massive and well-funded public health effort aimed at ridding the world of another mosquito-borne illness, malaria, provided an invaluable tool in Kazura’s fight. And, at no cost.

Ten years after villagers had received their last dose of treatment, the Global Fund began providing bednets. Kazura and his team measured transmission two years before the bednets were put in place and up to three years after.

“Even though the infection levels in people were lower than they had been in 1993 when we started to administer treatment, they were starting to come back, and if we did nothing we knew that probably in 10 years we would be exactly where we were when we started,” Kazura said.

But within months of putting the bednets in place, the total mosquito population dropped significantly, and of the mosquitoes they collected, not a single one was infected with the parasites. The effect lasted for two years and even longer in some areas.

“So before we used nets we thought the likelihood of stopping transmission was less than 5 percent,” Kazura said. “In some of the villages it went to greater than 95 percent likelihood of stopping transmission, even if we did nothing else at the present time.”

Just the bednets, he said, would be enough to potentially eliminate the disease in some populations. That’s very good news for countries that can’t afford mass drug treatment, or where the treatment just isn’t feasible.

It would still be ideal to use both mass drug treatment and the bednets, he said, and it will be the way his team treats populations now.

Does Kazura think that lymphatic filariasis can be wiped out in 7 years? He thinks so, but as most scientists do, he qualifies his answer.

“It depends on where you’re talking,” he said. “Around the areas where we’re working I think it’s certainly feasible. In remote areas, some of the problems are political. What do you do when there’s civil conflict? So global elimination may not be possible, but not because the right science isn’t there, but simply because you can’t do it for reasons of stability.”

The center’s lymphatic filariasis team recently won another NIH grant based on their research, and will focus now on different dosing and timing of drug treatment to see if any particular variation helps to reduce transmission of the disease.

Other recent grants awarded to center faculty will fund research on malaria, lymphatic filariasis, Schistosomiasis (snail fever), Rift Valley fever, and the use of antiretroviral drugs in newborns.

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